The major aim of this proposal is to investigate further the hypothesis that the macromolecular components of extracellular matrices (collagens and proteoglycans) are involved in the regulation of a number of developmental phenomena, including the differentiation of cartilage, muscle, cornea, neural crest derivatives, and palatal tissue. We propose to study the interactions that occur between collagens and proteoglycans by both biochemical (binding-aggregation assays, kinetics of fibrillogenesis, affinity column chromatography) and morphological (electron microscopic examination of defined matrices, autoradiography) procedures. Based on these findings, synthetic matrices of known compositions will be prepared in vitro and used to establish the effects of extracellular matrix macromolecules on a number of aspects of cell behavior, including cell adhesion, cell division, cell migration, and cell differentiation. These studies will help us gain insight into the role of extracellular matrix components in normal development, and how alterations in these macromolecules lead to disorders of development including the chondrodystrophies and such craniofacial anomalies as clefts of the secondary palate and abnormalities of the neural crest derivatives.